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4. Supplementation studies

Ultimately the test of whether specific mineral deficiencies may affect the growth and bone development of children in the developing world can only be answered with carefully controlled supplementation studies. To date there have been relatively few such investigations, and most have involved supplementation with either Zn or Ca. Those studies in which growth has been used as an outcome indicator are summarised in Tables 6-8. Zn supplementation studies of Western children have been included in Table 6 because of the similarity of their Zn intakes to those of Third World children.

It is difficult to generalise the results of the supplementation studies because of wide differences in treatments used, subject ages, social class and home diet, and because many of the investigations, although controlled, were not randomised or double-blind. Despite this, the accumulating evidence suggests that Zn supplementation can increase the height and weight gains of certain groups, particularly infant and adolescent boys, in both developed and developing countries. The response may be limited to individuals with pronounced growth-faltering or low plasma/hair Zn levels. Whether the effect of Zn is a direct consequence of improving Zn supply for tissue growth and metabolism, or is mediated through stimulation of the appetite is unclear.

Table 6. Controlled Zn supplementation studies of well children

Unless stated all children continued with their normal diet during study.

M = male, F = female
S = supplement, no extra zinc, Zn = supplement plus extra Zn. Diet = dietary intake.
+ = significant effect, 0 = no significant effect.
^a Subjects: GR = growth retarded, SE = socioeconomic class, Low Zn = low plasma/hair Zn.
^b Subjects with hair Zn <1.68 mmol/g.
^c BF = breast-fed (+ undescribed weaning foods).
^d Children with heights below the 3rd centile.
^e Protein, vitamin and micronutrient supplement with and without added Zn.
^f Bone = length, width, medullary width of second metacarpal.
^g Liquid protein and vitamin supplement with and without added Zn.
^h FF = formula fed (Similac + iron @ 1.8 mgZn/l).
ⁱ 5.8 mg/l formula milk.
^j Children with failure to thrive.

Table 7. Zinc supplementation studies of severely malnourished children

Mal = mixed marasmus, kwashiorkor, marasmic-kwashiorkor, Mar = marasmus, Kwa = kwashiorkor. The zinc dose was added to the rehabilitation diet, except where stated.

^a zinc dose given per kg body weight per day.
^b Home diet supplemented with vitamins.
^c Advantage in length gain seen at 30 d only.
^d Dose given per kg feed.
^e Children given a high protein diet.

The results of Zn supplementation are more dramatic for children, male and female, recovering from severe malnutrition when growth is extremely rapid and requirements are much greater than normal (Table 7). This is discussed in more detail elsewhere in this volume. Zn supplementation of customary rehabilitation diets not only improves weight gain but produces proportionately greater deposition of lean tissue (Golden & Golden, 1992). An increase in length gain was noted in one study (Schlesinger et al., 1992). In addition, Zn treatment of young children recovering from severe diarrhoea has been shown to enhance length gains (Behrens, Tomkins & Roy, 1990).

The main impression from the few available Ca studies is that supplementation with Ca alone or together with P has little impact on growth velocity but may correct biochemical indicators of marginal Ca status (Table 8). Exceptions are the studies of Indian children by Aykroyd and Krishnan (1938, 1939) in which significant differences in height and weight gain over 3-5 months were observed between control children and those supplemented with relatively low doses of Ca. The differences in height gain were small (3-6 years: 0.14 inches, 6-12 years: 0.21 inches). It has been speculated that the results could be explained by stimulation of the appetite by the calcium salt with consequent increases in food intake (Walker, 1954).

In addition to controlled studies with calcium salts, there have been a number of investigations in which calcium-rich or calcium-enriched foods have been provided. For example, improved growth after supplementation with animal milks and with Ca-enriched dhokla (fermented batter) have been reported (Aykroyd & Krishnan, 1937; 1939; Rajalakshmi et al., 1973; Vaughan et al., 1981). These studies are difficult to interpret in terms of an improved Ca supply as the results probably reflect increases in total food intakes rather than the correction of a putative Ca deficiency.

Table 8. Controlled calcium supplementation studies in children from developing countries with low-medium calcium intakes